cytochalasin-e and Abnormalities--Drug-Induced

Adult toxicity, embryo lethality, and teratogenicity of cytochalasins D and E (CD and CE) were determined for A/J, C57BL/6JH, aeae, and OELN mouse strains. The adult LD50 for CD (1.9-2.6 mg/kg) and CE (3.1-3.3) were similar for the strains. Although adult LD50s were similar, the embryo lethality and teratogenicity of CD and CE vary from strain to strain when all were treated with intraperitoneal injections on days 7-9 of gestation. CD was more teratogenic than CE and frequently produced exencephaly while CE did not. CD was more teratogenic in OELN and aeae (ED50 +/- 0.7 mg/kg) than in A/J or C57BL/6J (ED50 greater than 1.2 mg/kg). OELN fetuses were more resistant to lethal effects of CD than the other strains which had fetal LD50s +/- 1.2 mg/kg maternal weight. The F1 fetuses of a cross of sensitive aeae and resistant C57BL/6J showed intermediate sensitivity to exencephaly. The results suggest a genetic contribution to the response and differences in action of CD and CE as teratogens.

Topics: Abnormalities, Drug-Induced; Animals; Cytochalasin D; Cytochalasins; Dose-Response Relationship, Drug; Lethal Dose 50; Mice; Mice, Inbred A; Mice, Inbred C57BL; Neural Tube Defects; Skull